Synaptic transmission at the neuromuscular junction involves the release of acetylcholine (ACh) at the nerve terminal and the sensing of this molecule by specific ACh receptors in the postsynaptic membrane of the muscle. The objective of this project is to initiate an inquiry into the cellular basis for the formation postsynaptic ACh receptor aggregates in response to innervation. Cultures of embryonic Xenopus nerve and muscle cells will be used in this study. We will use histochemical techniques involving the derivatives of alpha-bungarotoxin to visualize clusters of ACh receptors. Light and electron microscopy will be conducted to examine the development of these clusters in both innervated and noninnervated muscle cells. First, we will examine the incorporation of new receptors and the lateral redistribution of existing receptors in contributing to the subsynaptic receptor population. Secondly, we will examine the mechanism which anchors receptors within a cluster against back diffusion. Thirdly, we will study the mechanism for the concentration of receptors into high-density aggregates based on the concept of membrane uptake. Fourthly, we will examine the relationship between receptor clusters and cytoxskeleton in an attempt to identify the cellular machinery for the aggregation. Finally, we will test a possible mechanism which brings about the exact registration of presynaptic transmitter release sites and postsynaptic receptor clusters, viz. gap junction between developing nerve and muscle. Overall, these studies should provide a framework for the understanding of the development of postsynaptic membrane during synaptogenesis. This may lead us to a fundamental understanding of the causes of certain developmentally or receptor-related neuromuscular disorders. Since receptors for other environmental or endogenous signals reside in nearly every cell, this study will also provide new insight into the general behavior of receptors in other cell types.